B6-100 CBCL Adrenal Incidentaloma Flashcards
most superficial layer of the adrenal cortex
zona glomerulosa
middle layer of the adrenal cortex
zona fasciculata
deepest layer of the adrenal cortex
zona reticularis
medulla is made up of […] tissue
neural
the adrenal cortex is made up of […] tissue
glandular cuboidal epithelial tissue
low blood pressure cause the JG cells in the kidneys produce
renin
renin converts […] to […]
angiotensinogen to angiotensin I
converts angiotensin I to angiotensin II
ACE
angiotensin II goes to the zona glomerulosa and binds to a […]
G coupled protein receptor
describe how G coupled protein receptor activation leads to the activation of pkA
**may not be super relevant to this exam, but step review
angiontensin II binds to G-coupled protein receptor
stimulates adenylate cyclase
adenylate cyclase –> GTPase
GTPase converts GTP to GDP to produce ATP
ATP –> cAMP
cAMP activates protein kinase A
cells that are very sensitive to sodium and potassium changes reside in what part of the adrenal cortex?
zona glomerulosa
stimulate the zona glomerulosa to produce aldosterone [3]
low bp
hyponatremia
hyperkalemia
CRH is secreted from the
hypothalamus
CRH stimulates […] to secrete ACTH
corticotropes
ACTH binds to the adrenal cortex via […]
G coupled protein receptor
inhibits aldosterone synthesis (biologic substance, not a medication)
atrial natriuretic peptide
causes hyperpolarization of the cell resulting in potassium efflux out of the cell
inhibits aldosterone synthesis
ANP
hormone synthesis requires […] as the basic unit
cholesterol
[cholesterol pathway]
cholesterol is converted to […]
pregnenolone
[cholesterol pathway]
pregnenolone can be converted to […] [2]
progesterone
17-hydroxypregnenolone
[cholesterol pathway]
progesterone can be converted to […] [2]
11-deoxycorticosterone
17-hydroxypregnenolone
converts progesterone to 11-deoxycorticosterone
21-hydroxylase
[cholesterol pathway]
11-deoxycorticosone is converted to
corticosone
[cholesterol pathway]
corticosone is converted to
aldosterone
transportation proteins of cortisol [2]
CBG (aka transcortin)
albumin
aldosterone acts on what part of the nephron?
DCT
aldosterone binds to intracytosolic receptors to induce what changes?
upregulates:
NaKATPase in basolateral membrane
ENaC channels
K+ channels
overall effect: more sodium reabsorption –> more water reabsorption, more K+ excretion —-> increased blood pressure
what is the outer layer of the adrenal cortex?
zona glomerulosa
what is the middle layer of the adrenal cortex?
zona fasiculata
what tissue is the adrenal medulla made of?
neural tisse
what do JG cells produce?
renin
where does ACE come from?
lungs
what are the effects of aldosterone? [4]
increase bp
increase blood volume
increase serum sodium serum
decrease serum K+
ANP inhibits what?
ACTH
the […] in the hypothalamus triggers the release of CRH
paraventricular nucleus
ACTH is a strong stimulus for […] synthesis
cortisol
effect of cortisol in muscle
activates transcription factors to increase proteases in cell
proteases stimulate protein catabolism, releasing amino acids in to the bloodstream to go to liver
effects of cortisol on adipose
induces lipolysis
trigylcerides broken down to fatty acids and glycerol
effects of cortisol on the liver
activates transcription factors to induce gluconeogenesis and glycogenolysis
where do the factors required for gluconeogenesis come from?
amino acids and lactic acid from muscle
glycerol and fatty acids from adipose
process where glucose is converted to glycogen
glycogenesis
cortisol directly stimulates […] in the liver [2]
glycogenesis
gluconeogenesis
cortisol indirectly stimulates […] in the liver
glycogenolysis
**increases the sensitivity of adrenergic receptors for norepinephrine
cortisol increases the sensitivity of adrenergic receptors for
norepinephrine
how does cortisol affect blood vessels?
increases the sensitivity of adrenergic receptors for norepinephrine (basically magnifies the effect of NE)
vasoconstriction
increase blood pressure
how does cortisol effect the immune system?
inhibits inflammatory response
stimuli of cortisol [2]
hypoglycemia
chronic stress
cortisol responds to hypoglycemia by [3]
directly stimulating gluconeogenesis and glycogenesis
indirectly stimulating glycogenolysis
long term chronic stress can causes a direct release of CRH, leading to
excessive production of ACTH —> cortisol
cortisol responds to chronic stress by [3]
vasoconstriction –> HTN
muscle catabolism
depresses immune system
increased cortisol in the blood exerts […] on the hypothalmus to decrease CRH
negative feedback
decreased cortisol triggers the hypothalamus to
PVN—> more CRH
pituitary —> more ACTH
[cholesterol pathway]
17-hydroxypregnenolone is converted to
androstenedione
androstenedione effect on the testes and ovaries [3]
increases libido
development of secondary sex characteristics
stimulates sebaceous glands
**minimal amounts get converted to estrogen and testosterone respectively
mineralcorticoids are secreted by
zona glomerulosa
glucocorticoids are secreted by
zona fasciculata
androgens are secreted by the
zona reticularis
catecholamines are secreted by the
medulla
how does the hypothalamus stimulate catecholamine release?
stimulates the SNS to send potential to the lateral gray cord at Th1 to L2 —> ventral ramus —> adrenal medulla
thoracolumbar outflow
describe the catecholamine pathway
tyrosine to L-DOPA
L-DOPA to dopamine
Dopamine to norepinephrine
norepinephrine to epinephrine
enzyme in the adrenal medulla that converts norepinephrine to epinephrine
PNMT
epinephrine binds to the liver via G coupled protein receptor to induce [2]
glycogenolysis
gluconeogenesis
results in hyperglycemia
catecholamine’s effect on the adipose tissue
binds to HSL to induce lipolysis
catecholamine effects on the heart
stimulate the expression of b1 receptors and cells of the SA and AV node to increase blood pressure by increasing contractility and constricting vessels
the effects of catecholamines on the respiratory system
dilates bronchioles
CRH stimulates corticotropes to release
ACTH
main mineralcorticoid secreted by zona glomerulosa
aldosterone
[…] inhibits the zona glomerulosa
ANP
stimuli for the zona glomerulosa to secrete aldosterone [4]
ACTH
angiotensin II
hyponatremia
hyperkalemia
main glucocorticoid secreted by the zona fasciculata
cortisol
the main androgens secreted by the zona reticularis [2]
dehydroepiandrostene (DHEA)
androstenedione
the […] is stimulated by the SNS through thoracolumbar output
adrenal medulla
main catecholamines secreted by the adrenal medulla
epinephrine
norepinephrine
general effects of catecholamines
increase blood pressure
increase glycogenolysis
increase gluconeogenesis
increase lipolysis
aldosterone stimulates [2]
Na+ reabsorption
K+ excretion
effects of cortisol [5]
suppresses immune system
stimulates protein catabolism in muscle
stimulates lipolysis
stimulates gluconeogenesis
increases b-1 adrenergic receptors
androgens act as precursors to [2]
estrogen and testosterone
increased levels of cortisol in the blood decrease the production of [2]
CRH
ACTH
low levels of cortisol in the blood stimulates [2]
PVN in hypothalamus to produce CRH
anterior pituitary to produce ACTH
CRH stimulates the
anterior pituitary
ACTH stimulates what part of the adrenal gland? [2]
zona fasciculata
zona reticularis
is aldosterone stimulated by ACTH?
no
a defect in the adrenal cortex results in a deficiency of [3]
cortisol
aldosteron
DHEA
a defect in the pituitary results in a deficiency of what hormones released from the adrenal gland? [2]
cortisol
DHEA
**not aldosterone
JG cells of the kidney release […] in response to low circulating blood volume
renin
produces angiotensinogen
liver
angiotensinogen is converted to angiotensin I in the blood by […]
renin
angiotensin I is converted to angiotensin II by […], which is produced in the […]
ACE
lungs
angiotensin II binds to receptors on the zona glomerulosa to stimulate […] production
aldosterone
addison’s is a […] renal insufficiency
primary
adrenal cortex is diseased, and the pituitary/hypothalamus is healthy
primary adrenal insufficiency
**addisons
addison’s disease results in the drop of […] hormones
all 3
cortisol
DHEA
aldosterone
most common cause of Addison’s disease
autoimmune
expected ATCH and cortisol levels in primary adrenal insufficiency
ACTH high
cortisol low
adrenal cortex healthy
pituitary diseased
secondary adrenal insufficiency
common causes of secondary adrenal insufficiency [2]
tumor/trauma
chronic steroid therapy
how does chronic long term steroid therapy cause secondary adrenal insufficiency?
steroids suppress ACTH production –>
adrenal cortex atrophies, preventing cortisol secretion
so when steroid is d/c the pituitary increases ACTH but there is no response from the adrenal gland due to atrophy
[cushing disease or syndrome]
caused by increased cortisol production from tumors or hyperplasia
cushing’s syndrome
[cushing disease or syndrome]
increased ACTH from the pituitary hyperstimulates the adrenal cortex causing increased cortisol
cushing’s disease
causes of cushings syndrome [2]
tumors
chronic steroid use
causes of cushings disease [2]
pituitary adenoma
ectopic ACTH producing cancer
common causes of ectopic ACTH secreting tumors
small cell lung cancer
renal cell carcinoma
pancreatic islet cells tumor
what is the normal response to low dose dexamethasone suppression test?
1 mg dexamethasone should suppress ACTH production and cortisol level
if you draw ACTH and it is increased this indicates a tumor where?
pituitary or ectopic ACTH secreting
if you draw ACTH and it is decreased this indicates what pathology?
adrenal tumor
or exogenous steroid consumption
how would a pituitary tumor respond to high dose (8mg) dexamethasone?
ACTH and cortisol would decrease
how would an adrenal tumor respond to high dose (8mg) dexamethasone?
no response, cortisol will remain high
treatment for pituitary adenoma
transsphenoidal resection
treatment for adrenal adenoma [2]
ketoconazole
adrenalectomy
the majority of adrenal adenomas are [functional/nonfuctional]
nonfunctional
**less than 10% are functional
tuberculosis can have what effect on the adrenal system?
adrenal insufficiency
clinical manifestions of adrenal insufficiency
skin hyperpigmentation
nausea/vomiting
weight loss
fatigue
orthostatic hypertension
expected labs in primary adrenal insufficiency
low cortisol
elevated plasma ACTH
low aldosterone
why does the adrenal medulla preferentially release epinephrine?
expresses PNMT which converts NE to Epi
does Cushing’s disease increase CRH?
no
the pituitary adenoma secretes ACTH independent of CRH
enzyme that converts cortisol to cortisone, inactivating it
11beta-hydroxysteroid dehydrogenase (11betaHSD)
the right adrenal gland drains into the
inferior vena cava
the left adrenal gland drains into the
left renal vein
the three arteries that supply adrenal glands
superior suprarenal from phrenic
middle suprarenal from aorta
inferior suprarenal from renal arteries
an individual with pheochromocytoma should be treated for […] with beta/alpha blockers prior to surgery
two weeks
nonselective inhibitor of adrenal and gonadal steroids
ketoconazole
medication used to treat hyperaldosteronism
spironolactone
aldosterone receptor antagonist
spironolactone
characterized by hypersecretion of aldosterone from the zona glomerulosa
Conn syndrome
classic presentation of Conn syndrome
refractory HTN
hypokalemia
metabolic alkalosis
signs of Addison’s disease
orthostatic hypotension
weight loss
skin hyperpigmentation
salt cravings
hyponatremia
hyperkalemia
autoimmune process that destroys the adrenal cortex
addison disease (primary adrenal insufficiency)
ACTH would be […] in Addison’s disease
elevated
[…] triggers the release of catecholamines from the adrenal medulla
acetlycholine
most common cause of congenital adrenal hyperplasia
21-hydroxylase deficiency
virilized genital
hypotension
hyperkalemia
hyponatremia
congenital adrenal hyperplasia
what laboratory results would be expected in 21- hydroxylase deficient congenital adrenal hyperplasia?
elevated 17-hydroxyprogesterone
hyperkalemia
hyponatremia
tumor of the adrenal medulla that oversecrete catecholamines
pheochromocytoma
best initial test for diagnosis of pheochromocytomas
24 urine measurement of metanephrines
episodic hypertension
palpitations
headaches
perspiration
increased catecholamine secretion (pheochromocytoma)
patients with pheochromocytoma should be give a-antagonists and b-blockers prior to surgery to prevent ….
unopposed a-adrenergic vasoconstriction causing
hypertensive crisis
cushing syndrome is caused by abnormally elevated […]
cortisol
cortisol is secreted from the zona […]
fasiculata
symptoms of cushing’s syndrome
hypertension
truncal obesity with striae
skin thinning
AMS
salt water wasting
ambiguous female genitalia in females
congenital adrenal hyperplasia
[…] deficiency is most common in CAH
21-hydroxylase
the adrenal medulla contain […] cells
chromaffin
chromaffin cells secrete [3]
epinephrine
norepinephrine
enkephalin
the majority of neuroblastomas in children are […]
sporadic
neuroblastoma tumors require […] testing
N-MYC
adrenal medullary tumor often presenting with HTN
pheochromocytoma
screening for […] in pheochromocytoma patients is recommended
most common germline mutations
eosinophilic laminated cytoplasmic inclusions indicated treatment with
spironolactone
what are urine metanephrines?
metabolites of catecholamines
**useful for evaluation of pheochromocytomas
what tests may be useful in the workup of pheochromocytomas?
metanephrines and normetanephrines
serum ACTH
urine cortisol
salivary cortisol
dexamethasone suppression
most likely underlying cause for an asymptomatic small adrenal nodule found incidentally
non functioning adrenal cortical adenoma
most common cause of cushing’s syndrome
exogenous glucocorticoids
best first step in evaluation of cushing’s syndrome
medication history
most common cause for malignant adrenal gland tumor?
metastatic tumors to the adrenal gland
metabolites of catecholamines [2]
vaillylmandelic acid
homovanillic acid
catecholamine secreting tumors [2]
pheochromocytomas
neuroblastoma
patients with adrenal suppression should be given […] prior to surgery to prevent shock
hydrocortisone
hypertension and hypokalemia are hallmark symptoms of
hyperaldosteronism
gluacoma
osteoporosis
diabetes
are symptoms of
prolonged steroid use
confirmatory test for hyperaldosteronism
24-urine collection of aldosterone
initial medical treatment of hyperaldosteronism
spironolactone
labile hypertension, diaphoresis, adrenal mass
pheochromocytoma
confirmatory test for diagnosis of pheochromocytoma
plasma metanephrines and normetanephrine
a minimum of […] tests are necessary to diagnose cushings
2
first line imaging for ACTH dependent Cushings
MRI pituitary
metanephrine and normetanephrine are derived from what amino acid?
tyrosine
imaging that is sensitive and specific for pheochromocytoma
MRI abdomen
screening tests for cushings [3]
24-urine cortisol
late night salivary cortisol
dexamethasone suppression
findings of Cushing’s syndrome
Metabolic syndrome (HTN, hyperglycemia, hyperlipidemia)
Obesity
Osteoporosis
Neuropsychotic (depression, anxiety, irriability)
Facial plethora
Androgen excess (acne, hirsutism)
Cataracts
Immunosuppression
Ecchymoses
Skin changes (thinning, striae, hyperpigmentation)
MOON FACIES
presents as hypertension with
XY: atypical genitalia, undescended testes
XX: lack of secondary sex characteristics
CAH - 17a-hydroxylase deficiency
presents in infancy with severe hypertension
virilization in females
CAH - 11b-hydroxylase deficiency
in CAH, if the deficient enzyme starts with 1 it causes
HTN
in CAH, if the deficient enzyme ends with 1 it causes
virilization in females
decreased androstenedione on labs indicates CAH with what deficiency?
17-a hydroxylase
increased renin and 17-hydroxyprogesterone on labs indicates CAH with what deficiency?
21-hydroxlase
decreased renin activity on labs indicates CAH with what deficiency?
11b-hydroxylase
exogenous glucocorticoids can cause reactivation of
TB
most common tumor of the adrenal medulla in children
neuroblastoma
tumor originating from neural crest cells
neuroblastoma
decreased plasma renin activity
elevated blood pressure
primary hyperaldosteronism
most common cause of primary hyperaldosteronism
idiopathic
**adrenocorticol neoplasms (Conn syndrome) is second
genetic associations with adrenal carcinomas
Li Fraumeni (p53 mutation)
Lynch syndrome
MEN1
FAP
NF1
Beckwith Wiederman
CAH
benign tumors composed for mature fat and hematopoietic elements
adrenal myelolipoma
caused by aldosterone secreting adenoma
Conn syndrome
most common cause of hypercortisolism
exogenous steroids
neoplastic causes of hypercortisolism [3]
- pituitary adenoma (cushings disease)
- ectopic ACTH
- adrenal tumor secreting cortisol
elevated ACTH
no reaction to low dose dexamethasone suppression, but eventually responds to high dose by suppressing ACTH
pituitary adenoma
elevated ACTH
no response to low or high dose dexamethasone
ectopic ACTH secreting tumor
low ACTH
no response to low or high dose dexamethasone
adrenal tumor independently secreting cortisol
most common cause of endogenous hypercortisolism
ACTH secreting pituitary adenomas
5 Ps of pheochromocytoma
Pressure (episodic HTN)
Pain
Perspiration
Palpitations
Pallor
headache
sweating
palpitations
pheochromocytoma
alpha blockers [2] and beta blocker [1] Keim listed in her slides for pheochromocytoma presurgical treatment
a: phenoxybenzamine, prazosin
b: propranolol
treatment for pituitary adenoma
transsphenoidal resection
treatment for adrenal adenoma
laparoscopic resection
medication used if treatment is not an option for adrenal Cushing’s
ketoconazole
when a patient with adrenal insufficiency is sick, […] the current steroids for three days
double
if a patient with adrenal insufficiency is having major surgery, what should be done?
change to IV steroids (hydrocortisone) during the time of critical illness
